生物信息学2024,Vol.22Issue(2):124-133,10.DOI:10.12113/202203007
抑郁症易感基因和抗抑郁药物靶点相关神经细胞类型及相互作用网络分析
Identification of neuronal cell types and interaction network of susceptibility genes of depressive disorder and antidepressant drug targets
摘要
Abstract
Our study is based on the genome-wide association analysis(GWAS)of depressive disorder,of which single nucleotide polymorphisms(SNPs)are retrieved and annotated by Haploreg software and 102 susceptibility genes are obtained by annotation of SNPs.Then gene-level analysis is performed on the summary statistics of GWAS by MAGMA software,and 270 significant genes are obtained after correction.Finally,a total of 320 susceptibility genes are obtained.Besides,133 antidepressant drug target genes are obtained from Drugbank.Then EWCE package is used to analyze cell type enrichment of susceptibility genes of depressive disorder and antidepressant drug targets in three dataset of brain tissue single-cell sequencing data respectively,and the results show that GABA neurons(inhibitory neurons)and glutamatergic neurons(excitatory neurons)in the cerebral cortex are the common neurons for susceptibility genes of depressive disorder and antidepressant drug targets,antidepressant drugs may be interacted with susceptibility genes of depressive disorder in these two types of neurons,besides,oligodendrocyte precursor cells may be specific susceptible nerve cells for depressive disorder.Network Calculator software is used to construct the network and conduct network topology parameter analysis and the results show that susceptibility genes of depressive disorder and antidepressant drug targets form a network with significant interactions.Our study provides insights for understanding the genetic mechanism of depressive disorder on the single-cell level,as well as investigation of new drug targets by network biology.关键词
单细胞测序/抑郁症易感基因/抗抑郁药物靶点,神经细胞/相互作用网络Key words
Single-cell RNA sequencing/Susceptibility genes of depressive disorder/Antidepressant drug targets/Neuronal cell/Interaction network分类
生物科学引用本文复制引用
赵弘毅,丁伟健,冯飞翔,宋文正,刘书齐,高蕾..抑郁症易感基因和抗抑郁药物靶点相关神经细胞类型及相互作用网络分析[J].生物信息学,2024,22(2):124-133,10.基金项目
山东省大学生创新创业训练计划项目(No.S202010439097) (No.S202010439097)
山东省医药卫生科技发展计划项目(No.2019WS391) (No.2019WS391)
山东省自然科学基金项目(No.ZR2020MC061). (No.ZR2020MC061)